Mismatch Negativity and Cognitive Performance for the Prediction of Psychosis in Subjects with At-Risk Mental State

Abstract

BackgroundA shorter duration of untreated psychosis has been associated with better prognosis in schizophrenia. In this study, we measured the duration mismatch negativity (dMMN), an event-related potential, and cognitive performance in subjects with at-risk mental state (ARMS), patients with first-episode or chronic schizophrenia, and healthy volunteers. The main interest was to determine if these neurocognitive measures predict progression to overt schizophrenia in ARMS subjects.Methodology/Principal FindingsSeventeen ARMS subjects, meeting the criteria of the Comprehensive Assessment of At-Risk Mental State, 31 schizophrenia patients (20 first-episode and 11 chronic) and healthy controls (N = 20) participated in the study. dMMN was measured by an auditory odd-ball paradigm at baseline. Neuropsychological performance was evaluated by the Japanese version of the Brief assessment of cognitive function of schizophrenia (BACS-J). The first-episode schizophrenia group showed significantly smaller amplitudes at frontal electrodes than did control subjects whereas chronic patients elicited smaller amplitudes at frontal and central electrodes, consistent with previous reports. During the follow-up period, 4 out of the 17 ARMS subjects transitioned to schizophrenia (converters) while 13 did not (non-converters). Specifically, dMMN amplitudes of non-converters did not differ from those of healthy controls, while converters showed significantly smaller dMMN amplitudes at some electrodes compared to control subjects. Converters performed significantly worse on tests of working memory, verbal fluency, and attention/information processing than did non-converters. There was a significant positive correlation between dMMN amplitudes at the frontal electrodes and verbal fluency, as measured by the BACS, in the AMRS subjects as a whole.Conclusions/SignificanceARMS subjects who later developed schizophrenia elicited smaller dMMN amplitudes to begin with, compared to non-converters. Notably, we have provided the first evidence for the ability of verbal fluency to predict dMMN amplitudes in ARMS subjects. These findings are expected to add to the efforts for early diagnosis and intervention of schizophrenia.

Equivalent mismatch negativity deficits across deviant types in early illness schizophrenia-spectrum patients

“…This is consistent with previous studies of recent onset schizophrenia (Atkinson et al, 2012; Higuchi et al, 2013; Jahshan et al, 2012; Javitt et al, 2000b; Oades et al, 2006; Perez et al, 2014; Todd et al, 2008; Umbricht et al, 2006), providing further evidence that auditory deviance processing is abnormal early in the illness course. Our results are consistent with other recent onset schizophrenia studies showing reduced MMN in response to long duration (Higuchi et al, 2013; Jahshan et al, 2012; Javitt et al, 2000b; Perez et al, 2014; Todd et al, 2008; Umbricht et al, 2006), frequency (Devrim-Ucok et al, 2008; Javitt et al, 2000b; Perez et al, 2014; Salisbury et al, 2007; Umbricht et al, 2006), frequency + duration combination (Perez et al, 2014), and intensity (Todd et al, 2008) auditory deviants. However, our results are inconsistent with some studies showing normal frequency-deviant MMN in recent onset (Todd et al, 2008) or first episode samples (Devrim-Ucok et al, 2008; Magno et al, 2008; Mondragon-Maya et al, 2013; Salisbury et al, 2002; Valkonen-Korhonen et al, 2003).…”

Contributions of early cortical processing and reading ability to functional status in individuals at clinical high risk for psychosis

“…Such studies have demonstrated consistent reductions of MMN in CHR individuals, albeit of smaller magnitude (typically 0.6-0.8 SDs vs. controls) than those observed in schizophrenia(Atkinson et al, 2012; Bodatsch et al, 2011; Higuchi et al, 2013; Jahshan et al, 2012; Perez et al, 2013; Shaikh et al, 2012; Solis-Vivanco et al, 2014). In addition, reductions in MMN amplitudes significantly predict conversion to psychosis among CHR individuals(Atkinson et al, 2012; Bodatsch et al, 2011; Higuchi et al, 2013; Perez et al, 2013; Shaikh et al, 2012). However, a relationship between MMN and functioning in this vulnerable population has remained relatively unexplored.…”

Mismatch negativity is a breakthrough biomarker for understanding and treating psychotic disorders

“…Perez et al (21) extended these findings to show that MMN amplitude also "forecasts" the time lag to psychosis onset in CHR individuals; those with more severe MMN abnormalities had shorter times to psychosis. These CHR and related studies (21,(23)(24)(25)(26) draw attention to the importance of identifying early biologic markers of disease vulnerability for predicting the development of psychosis and enhancing individualized risk-estimation/ prevention strategies (20).…”